title: Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism.
abstract: BACKGROUND
  Preclinical studies suggested the existence of a signaling pathway connecting bone and glucose metabolisms. Supposedly leptin modulates osteocalcin bioactivity, which in turn stimulates insulin and adiponectin secretion, and β-cell proliferation.
  
  
  OBJECTIVE
  The objective of the investigation was to study the reciprocal relationships of adiponectin, leptin, osteocalcin, insulin resistance, and insulin secretion to verify whether such relationships are consistent with a signaling pathway connecting bone homeostasis and glucose metabolism.
  
  
  METHODS
  This was a cross-sectional analysis.
  
  
  METHODS
  The study was conducted with community-dwelling volunteers participating in the Baltimore Longitudinal Study of Aging.
  
  
  METHODS
  Two hundred eighty women and 300 men with complete data on fasting plasma adiponectin, leptin, and osteocalcin, oral glucose tolerance test (plasma glucose and insulin values available at t = 0, 20, and 120 min), and anthropometric measures participated in the study.
  
  
  METHODS
  Linear regression models were used to test independent associations of adiponectin, osteocalcin, and leptin with the indices of insulin resistance and secretion. The expected reciprocal relationship between different biomarkers was verified by structural equation modeling.
  
  
  RESULTS
  In linear regression models, leptin was strongly associated with indices of both insulin resistance and secretion. Both adiponectin and osteocalcin were negatively associated with insulin resistance. Structural equation modeling revealed a direct inverse association of leptin with osteocalcin; a direct positive association of osteocalcin with adiponectin; and an inverse relationship of osteocalcin with insulin resistance and adiponectin with insulin resistance and secretion, which is cumulatively consistent with the hypothesized model.
  
  
  CONCLUSIONS
  Bone and glucose metabolisms are probably connected through a complex pathway that involves leptin, osteocalcin, and adiponectin. The clinical relevance of such a pathway for bone pathology in diabetes should be further investigated.
authors.affiliation: National Institute on Aging, Clinical Research Branch, 3001 South Hanover Street, Baltimore, Maryland 21225, USA.
authors.forename: Kristofer S
authors.initials: KS
authors.lastname: Gravenstein
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Napora
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Short
authors.forename: Ramona
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Chee W
authors.initials: CW
authors.lastname: Chia
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D015675:Osteocalcin; D005947:Glucose